title: Single-dose liposomal amphotericin B (AmBisome®) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.
  
  
  METHODS
  An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose.
  
  
  CONCLUSIONS
  An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00832208.
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, UK.
authors.forename: Tansy
authors.initials: T
authors.lastname: Edwards
authors.forename: Raymond
authors.initials: R
authors.lastname: Omollo
authors.forename: Eltahir A G
authors.initials: EA
authors.lastname: Khalil
authors.forename: Sisay
authors.initials: S
authors.lastname: Yifru
authors.forename: Brima
authors.initials: B
authors.lastname: Musa
authors.forename: Ahmed
authors.initials: A
authors.lastname: Musa
authors.forename: Monique
authors.initials: M
authors.lastname: Wasunna
authors.forename: Peter G
authors.initials: PG
authors.lastname: Smith
authors.forename: Catherine
authors.initials: C
authors.lastname: Royce
authors.forename: Sally
authors.initials: S
authors.lastname: Ellis
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
mesh_terms: D000351:Africa, Eastern; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007898:Leishmaniasis, Visceral / Q000175:diagnosis / Q000188:drug therapy*; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B